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J Damas

Publications and source records attributed to J Damas.

214 records · Page 12Linked to original sources
PubMedDate not supplied

Involvement of platelet-activating factor in the hypotensive response to zymosan in rats.

In anaesthetised rats, intravenous injection of zymosan induced a reduction of serum complement haemolytic activity, leukopenia, thrombocytopenia, a decrease in blood pressure, an increase in haematocrit and paw oedema. Stimulation of platelets resulted in their accumulation in lungs and liver as shown by the distribution of 51Cr-labelled platelets. The hypotensive response to zymosan was largely inhibited by WEB 2086, a PAF antagonist. Plasma extravasation was reduced by WEB 2086, by the association of mepyramine and methysergide with ketoprofen or BW 755C. Paw oedema was increased by ketoprofen and abolished by the association of WEB 2086, BW 755C, methysergide and mepyramine. This treatment did not modify the leukopenia. Lipopolysaccharide produced a decrease in blood pressure and, at higher doses, a reduction of serum complement haemolytic activity. It is concluded that the vascular responses to intravascular complement activation by zymosan in rats depend mainly on the release of PAF. They are also mediated, for a small part, by eicosanoids and mast cell amines. Though zymosan and endotoxin induced similar PAF-dependent effects, the complement system is not involved in endotoxin shock in rats.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMedDate not supplied

Inhibition by WEB 2086, a PAG-acether antagonist of oedema and peritonitis induced by zymosan in rats.

WEB 2086 reduced the increase in vascular permeability induced by platelet-activating factor (PAF-acether) in rat abdominal skin. Injected alone, WEB 2086 did not modify the oedema induced by zymosan in rat paw. However, administered with methysergide and mepyramine, WEB 2086 reduced the development of this oedema during the first two hours. WEB 2086 also reduced the volume of the exudate induced by zymosan in the peritoneal cavity and its content in leucocytes. Methysergide and mepyramine reduced the volume of the peritoneal exudate. BW755C inhibited the peritoneal accumulation of fluid and of leucocytes. Indomethacin was inactive. The inhibitory effect of WEB 2086 suggests that PAF-acether is involved in the inflammatory responses induced by zymosan in rats beside other endogenous factors such as lipoxygenase products and mast cell amines.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMedDate not supplied

Involvement of PAF-acether in the anaphylactic shock in the rat.

In normal Wistar rats, SDZ 63-675 (1.2 mg/kg) inhibited hypotension and hemoconcentration induced by PAF-acether (0.2-0.8 micrograms/kg.min). These effects of PAF-acether were not modified by ketoprofen (3 mg/kg). Only the hemoconcentration was reduced by BW755C (40 mg/kg). Part of the vascular effects of PAF-acether in rats would thus depend on the release of lipoxygenase products. In sensitized rats, SDZ 63-675 (1.2 mg/kg) increased the survival rate, reduced the vascular collapse and suppressed the hemoconcentration induced by intravenous injection of the antigen. BW755C (40 mg/kg) increased the survival rate and slightly reduced the vascular collapse. This anaphylactic shock was neither modified by ketoprofen (3 mg/kg), acetylsalicylic acid (100-200 mg/kg) and indometacin (3-6 mg/kg) nor by the association of methysergide (3 mg/kg), metiamide (35 mg/kg) and mepyramine (3 mg/kg). The inhibitory effect of SDZ 63-675 on the anaphylactic shock was not affected by the association with methysergide, mepyramine and metiamide or with indometacin. It was enhanced by acetylsalicylic acid. Injected simultaneously, SDZ 63-675 and BW755C suppressed the vascular collapse induced by the antigenic challenge. The main vasoactive factors responsible for this anaphylactic shock in the rat would thus be, in decreasing order, PAF-acether, leukotrienes and prostanoids. The association of mepyramine, methysergide and metiamide inhibited hypotension and hemoconcentration induced by the infusion of dextran. Since SDZ 63-675 had no influence on the effects of dextran, it is concluded that dextran did not release significant amounts of PAF-acether from mast cells.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMedDate not supplied

Substituted phenylthiophenylamines with antiinflammatory activity.

Several acid and closely related non acid derivatives of 2-phenylthio- and 4-phenylthio-N-acyl phenylamines have been synthesized and tested in vivo, on the carrageenan RFE assay, and in vitro, on prostaglandin synthesis inhibition assay. Compound (XV c), bearing a propanoic acid substituent together with a p-chlorobenzoyl group situated on nitrogen atom in the 2-position, showed a 79% edema reduction (300 mg/kg p.o.) 6 hours after carrageenan injection, but no activity in vitro. The benzyl alcohols (XIV m) and (XIV n), on the contrary, inhibited PG synthesis; their lack of activity in vivo could be interpreted as the result of their oxidation to the inactive benzoic acids (XIV g) and (XIV h).

Aniline Compounds↗
PubMedDate not supplied

[The influence in the rat of counter-irritation by turpentine on the leukocyte content of exudates induced by sponge implants].

In normal rats, PGE1, arachidonic acid, indomethacin and diclofenac did not modify the leucocyte content of sponge exudates withdrawn 4 hours after implantation while arachidonic acid increased the level in PGE2 and indomethacin reduced it. The leucocyte content of sponges exudates withdrawn 18 hours after implantation was not modified by PGE1 and TXB2, but diminished by indomethacin and NDGA and increased by arachidonic acid. As the chemotactic effect of arachidonic acid was slightly reduced by indomethacin and abolished by NDGA, it could depend on the formation of lipoxygenase derivatives. In normal rats, the leucocyte content of sponge exudates withdrawn 18 hours after implantation was increased slightly by normal serum and largely by serum from turpentine-treated rats. The blood leucocyte content was not modified in turpentine-treated rats. However in these rats, the leucocyte content of sponge exudates was low comparatively to the leucocyte content in normal rats. This low level was not affected by indomethacin, arachidonic acid and normal serum. The leucocytes of turpentine-treated rats seem to be desensitizated towards chemotactic factors. Similar desensitization was observed in rats treated by iota carrageenan.

Animals↗
PubMedDate not supplied

[On the hypotensive activity of carrageenan iota in the rat (author's transl)].

1. Carrageenan iota and dextran sulfate deplete the plasmatic stores of kininogens in the Rat. 2. A slow intravenous infusion of carrageenan iota in the anaesthetized Rat produces a lowering of blood pressure which is only transient because of the development of tachyphylaxy. At this stage the cardio-vascular system which fails to respond to carrageenan iota injection is also refractory to ellagic acid administration. After depletion of the plasmatic stores of kininogens by dextran sulfate, glandular kallikreins or ellagic acid, carrageenan iota has lost its hypotensive properties. It is concluded that the cardio-vascular effects of carrageenan iota are mainly due to activation of the kininogenskinins system. 3. Indomethacin curtails the hypotensive effects of kinins by inhibition of the release of prostaglandins by these polypeptides. It also reduces the duration of the hypotensive response to carrageenan. Carrageenan iota is neither a histamine nor a 5-hydroxytryptamine liberator.

Albinism↗
PubMedDate not supplied

[Platelet stimulation and hypotensive action of carrageenans in the rat].

We studied the hypotensive effect of three carrageenans and of dextran sulphate in Brown Norway (BN) rats. The plasma of these BN rats is devoid of high molecular weight kininogen and poor in plasma prekallikrein. The hypotensive effect in BN rats was greatly reduced in comparison with the effects in normal rats. It was proportional to the thrombocytopenia induced by the sulphated polysaccharides and absent in rats made thrombopenic by antiplatelet serum. The hypotensive effect in BN rats was reduced by bromophenacyl bromide, mepacrine, aspirin, methysergide, promethazine and CCI 17810, and was unchanged after the administration of cobra venom factor, heparin, amino caproic acid, chloroquine, dexamethazone, lidocaine, propranolol, indomethacin, phenidone, imidazol, adenosine and cyproheptadine. The thrombopenic effect was reduced by methysergide and CCI 17810 and was not modified by bromophenacyl bromide and chloroquine.

Animals↗
PubMedDate not supplied

[Kinins and oedema induced by different carrageenans (author's transl)].

1. The oedema induced in the paw of the Wistar rat by local injection of three different carrageenans allows us to determine the inflammatory activity of these sulphated polysaccharides. This activity is greatest for the lambda type, it is reduced for the iota compound and is smallest for the kappa carrageenan. 2. Reduction of plasmatic stores of kininogens by ellagic acid or inhibition of kinin formation by hexadimethrine reduce the inflammatory reaction induced by the three carrageenans. Inhibition of kininases by phenanthroline increases the oedema. Thus the kinin system is involved in the development of this type of oedema. 3. In Brown-Norway rats, which lack of plasmatic kallikrein and kininogens, the inflammatory activity of the three carrageenans is very small. By comparing the activity in Wistar rats and in Brown-Norway rats, it is concluded that the kinin system is the most important factor in the development of the inflammatory reaction induced by the three types of carrageenans.

Animals↗
PubMedDate not supplied

Presence of immunoreactive platelet-activating factor in peritoneal exudate induced by zymosan in rats.

The presence of the platelet-activating factor (PAF) in peritoneal exudate, induced by zymosan, was investigated in rats. Intraperitoneal injection of zymosan induced an extravasation of plasma proteins and an accumulation of polymorphonuclear leukocytes in the peritoneal cavity. Zymosan induced a release of immunoreactive PAF in peritoneal exudate which reached maximum levels at 30 min and then declined slowly. Immunoreactive PAF was evenly distributed in the fluid and cellular fractions of the exudate. A PAF-acetyltransferase activity was found as well in the exudate as in plasma. Histamine levels, measured by bioassay, increased after injection of zymosan, reached a peak at 15 min and declined to a normal level within 4 hr. Protein extravasation was inhibited by WEB 2086, a PAF antagonist, during the 6 hours of the study, whereas the accumulation of leukocytes was suppressed at 2 hour by WEB 2086 and SM 12502, two PAF antagonists. PAF is present in the peritoneal exudate induced by zymosan in rats, and plays a role in the development of the inflammatory response. Its main origin might be resident macrophages and polymorphonuclear leukocytes.

Acetyltransferases↗
PubMedDate not supplied

Pharmacomodulation of torasemide led to original diuretic, neuroprotective, anticonvulsant and antithrombotic drugs.

Pharmacomodulation of torasemide, a diuretic sulfonylurea, led to the discovery of two novel diuretics, a sulfonylthiourea (BM 20) and a sulfonylcyanoguanidine (BM 106). BM 27, a lipophilic sulfonylurea, exhibited neuroprotective properties associated to an anticonvulsant activity. As BM 27, two lipophilic sulfonythioureas (BM 11 and BM 34) revealed an anticonvulsant profile similar to that of phenytoin. Finally the synthesis of torasemide derivatives led to the development of a sulfonylcyanoguanidine (BM 144) with a thromboxane A2 antagonist potency.

Animals↗